Instructions for Brufen retard tablets 800 mg No. 14
Composition
active ingredient: ibuprofen;
1 tablet contains 800 mg of ibuprofen;
excipients: xanthan gum, povidone, stearic acid, colloidal anhydrous silicon dioxide; tablet shell: hypromellose, talc, titanium dioxide (E 171).
Dosage form
Extended-release tablets, film-coated.
Main physicochemical properties: white, pillow-shaped tablets, film-coated.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Propionic acid derivatives. Ibuprofen. ATC code M01A E01.
Pharmacological properties
Pharmacodynamics.
Ibuprofen is a propionic acid derivative, a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic effects. The therapeutic effects of the drug are believed to be due to its inhibitory effect on the cyclooxygenase enzyme, which leads to a marked decrease in prostaglandin synthesis. These properties provide relief from symptoms of inflammation, pain, and fever.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid/aspirin on platelet aggregation when both drugs are used concomitantly. Some pharmacodynamic studies have shown that a single dose of ibuprofen 400 mg administered 8 hours before or within 30 minutes after immediate-release acetylsalicylic acid/aspirin (81 mg) reduced the effect of acetylsalicylic acid/aspirin on thromboxane formation or platelet aggregation. Although there is uncertainty regarding the extrapolation of the data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid/aspirin. Clinically significant effects are unlikely with irregular use of ibuprofen (see section 4.5).
Pharmacokinetics.
The pharmacokinetic profile of BRUFEN® RETARD in the dosage form of prolonged-release film-coated tablets compared to that of the drug in the dosage form of rapid-release tablets at a dose of 400 mg demonstrated that this prolonged-release dosage form (with delayed release) smoothes out the peak increases and decreases in the concentration of the active substance, which are characteristic of rapid-release tablets, and provides higher levels of the active substance at 5, 10, 15 and 24 hours. The area under the plasma concentration-time curve for the prolonged-release tablets was almost identical to that of the rapid-release tablets.
The mean plasma profiles and plasma levels before the next dose were not significantly different in young and elderly subjects. According to several studies, BRUFEN® RETARD has demonstrated a plasma profile with two peak concentrations when taken in the fasted state. The half-life of ibuprofen is approximately 2 hours. Ibuprofen is metabolized in the liver to two inactive metabolites, which are excreted by the kidneys together with unchanged ibuprofen in pure form or as conjugates. Renal excretion is rapid and complete. Ibuprofen is extensively bound to plasma proteins.
Indication
Rheumatoid arthritis (including juvenile rheumatoid arthritis or Still's disease), ankylosing spondylitis, osteoarthritis and other non-rheumatoid (seronegative) arthropathies.
Non-articular rheumatic and periarticular lesions, such as shoulder scapular periarthritis (capsulitis), bursitis, tendonitis, tenosynovitis and low back pain; soft tissue injuries, such as sprains and strains of ligaments.
For the relief of mild to moderate pain, such as dysmenorrhea, dental and postoperative pain, and for the symptomatic relief of headache, including migraine.
Contraindication
Known hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.
Ibuprofen should not be used in patients with a history of hypersensitivity reactions (e.g. asthma, urticaria, angioedema or rhinitis) following the use of ibuprofen, acetylsalicylic acid/aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).
Severe heart failure (IV functional class according to the New York Heart Association (NYHA) criteria).
Severe liver failure.
Severe renal failure (glomerular filtration rate <30 ml/min).
Conditions accompanied by an increased risk of bleeding or active bleeding.
History of gastrointestinal bleeding or perforation due to previous NSAID use.
Acute or history of ulcerative colitis, Crohn's disease, acute or recurrent gastric ulcer or gastrointestinal bleeding (2 or more separate episodes of confirmed ulceration or bleeding).
Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
Interaction with other medicinal products and other types of interactions
Caution is required when using the following drugs concomitantly due to possible drug interactions observed in some patients.
Antihypertensives, β-blockers, and diuretics. NSAIDs may reduce the effect of antihypertensive drugs such as ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and diuretics. Diuretics may also increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of cardiac glycosides.
Cholestyramine: Concomitant administration of ibuprofen and cholestyramine may reduce the absorption of ibuprofen from the gastrointestinal tract (GI). However, the clinical significance of this is unknown.
Lithium. NSAIDs may reduce lithium excretion.
Methotrexate: NSAIDs may inhibit the tubular secretion of methotrexate and reduce the clearance of methotrexate.
Cyclosporine: Increased risk of nephrotoxicity when used with NSAIDs
Mifepristone. A reduction in the efficacy of the medicinal product is theoretically possible due to the antiprostaglandin properties of NSAIDs, including acetylsalicylic acid. Limited data suggest that concomitant use of NSAIDs on the day of prostaglandin administration does not adversely affect the effect of mifepristone or prostaglandin on cervical ripening or uterine contractility and does not reduce the clinical efficacy of medical abortion.
Other analgesics/NSAIDs, including selective COX-2 inhibitors: The concomitant administration of two or more NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the increased risk of adverse reactions (see section 4.4).
Acetylsalicylic acid/aspirin. As with other NSAIDs, concomitant use of ibuprofen and acetylsalicylic acid/aspirin is generally not recommended due to the risk of increased adverse reactions.
Experimental data suggest that ibuprofen may competitively inhibit the effect of low-dose acetylsalicylic acid/aspirin on platelet aggregation when used concomitantly. Although there is uncertainty about the extrapolation of these data to the clinical situation, it cannot be excluded that regular long-term use of ibuprofen may reduce the cardioprotective effect of low-dose acetylsalicylic acid. Clinically significant effects are unlikely with irregular use of ibuprofen (see section "Pharmacological properties. Pharmacodynamics").
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding when administered with NSAIDs (see section "Special warnings and precautions for use").
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4).
Quinolone antibiotics: Animal data suggest that NSAIDs may increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones concurrently are at increased risk of seizures.
Sulfonylureas: NSAIDs may potentiate the effects of sulfonylureas. Hypoglycemia has been reported rarely in patients taking sulfonylureas during ibuprofen therapy.
Antiplatelet agents and selective serotonin reuptake inhibitors (e.g. clopidogrel and ticlopidine). Increased risk of gastrointestinal bleeding when taken with NSAIDs (see section "Special warnings and precautions for use").
Tacrolimus: There may be an increased risk of nephrotoxicity when NSAIDs are administered concomitantly with tacrolimus.
Zidovudine: NSAIDs increase the risk of hematological toxicity when administered concomitantly with zidovudine. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia when ibuprofen is administered concomitantly with zidovudine.
Aminoglycosides: NSAIDs may reduce the excretion of aminoglycosides.
Herbal extracts. Ginkgo biloba may potentiate the risk of bleeding associated with NSAIDs.
CYP2C9 inhibitors. Co-administration of ibuprofen with CYP2C9 inhibitors may increase the exposure of ibuprofen (a CYP2C9 substrate). In one study, voriconazole and fluconazole (CYP2C9 inhibitors) were shown to increase the exposure of S(+)-ibuprofen by approximately 80–100%. A reduced ibuprofen dose should be considered when co-administered with potent CYP2C9 inhibitors, especially when high doses of ibuprofen are administered with voriconazole or fluconazole.
Application features
General warnings
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time sufficient to control symptoms (see section “Dosage and Administration” and information on gastrointestinal and cardiovascular risks and masking of symptoms of underlying infections below).
With prolonged use of any painkillers, headaches may occur, which should not be treated with increased doses of the drug.
Concomitant use of NSAIDs with alcohol may increase the side effects associated with the active substance, particularly from the gastrointestinal tract or central nervous system.
Elderly patients have a higher incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Children
Children and adolescents with dehydration are at risk of kidney dysfunction.
Gastrointestinal bleeding, ulceration and perforation
NSAIDs should be used with caution in patients with a history of peptic ulcer and other gastrointestinal diseases, as their condition may be aggravated (see section "Contraindications").
Gastrointestinal bleeding, ulceration or perforation has been reported with all NSAIDs at any time during treatment. These adverse reactions may be fatal and may occur with or without life-threatening symptoms or a history of serious gastrointestinal disorders.
The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, particularly if complicated by bleeding or perforation (see section 4.3), and in the elderly. Such patients should start treatment with the lowest available dose. Consideration should be given to the concomitant use of protective agents (e.g. misoprostol or proton pump inhibitors) in such patients, as well as in patients taking concomitant low-dose acetylsalicylic acid/aspirin or other drugs that increase the risk of gastrointestinal damage (see below and section 4.5).
The use of ibuprofen with other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to an increased risk of ulceration or bleeding (see section "Interaction with other medicinal products and other types of interactions").
Patients, especially the elderly, with a history of gastrointestinal disease should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially during the initial stages of treatment.
Ibuprofen should be prescribed with caution to patients receiving concomitant treatment with drugs that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid/aspirin (see section "Interaction with other medicinal products and other forms of interaction").
If gastrointestinal bleeding or ulceration develops in a patient receiving ibuprofen, treatment with the drug should be discontinued.
Respiratory disorders
Ibuprofen should be prescribed with caution to patients with or with a history of bronchial asthma, chronic rhinitis, allergic diseases, as NSAIDs have been reported to cause bronchospasm, urticaria, or angioedema in such patients.
Impaired heart, kidney and liver function
The use of NSAIDs may cause a dose-dependent decrease in prostaglandin formation and lead to renal failure. Habitual concomitant use of such analgesics further increases this risk. Patients with impaired renal, cardiac or hepatic function, those taking diuretics and the elderly are at greatest risk of this reaction. In such patients, the lowest effective dose should be used for the shortest possible period of time and renal function should be monitored, especially in the case of long-term treatment (see section "Contraindications").
Ibuprofen should be administered with caution to patients with a history of heart failure or hypertension, as edema has been reported with ibuprofen use.
Cardiovascular and cerebrovascular effects
Appropriate monitoring and supervision are necessary in patients with a history of hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAID therapy.
Clinical studies suggest that ibuprofen, especially at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). Overall, epidemiological studies do not suggest an association between low-dose ibuprofen use (i.e. ≤ 1200 mg/day) and an increased risk of arterial thrombotic events.
Patients with uncontrolled hypertension, congestive heart failure (NYHA functional class II–III), diagnosed ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should be prescribed ibuprofen only after careful analysis of the situation, and high doses (2400 mg per day) should be avoided.
Cases of Kounis syndrome have been reported in patients treated with ibuprofen. Kounis syndrome is defined as cardiovascular symptoms caused by an allergic or hypersensitivity reaction associated with narrowing of the coronary arteries, potentially leading to myocardial infarction.
Kidney effects
Caution should be exercised when initiating ibuprofen treatment in patients with significant dehydration. There is a risk of renal impairment, especially in children, adolescents and elderly patients with dehydration.
As with other NSAIDs, prolonged use of ibuprofen may lead to renal papillary necrosis and other pathological changes in the kidneys. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal perfusion. The administration of NSAIDs to such patients may cause a dose-dependent decrease in prostaglandin formation and, as a result, a decrease in renal blood flow, which may lead to renal failure. Patients with impaired renal function, heart failure, liver dysfunction, patients taking diuretics and angiotensin-converting enzyme (ACE) inhibitors, as well as elderly patients, are at high risk of developing this reaction. Discontinuation of NSAIDs is usually accompanied by a return to the state that preceded treatment.
Renal tubular acidosis and hypokalemia may develop after acute overdose and in patients taking high doses of ibuprofen for a long period (usually longer than 4 weeks), including doses exceeding the recommended daily dose.
Systemic lupus erythematosus and mixed connective tissue diseases.
Patients with systemic lupus erythematosus and mixed connective tissue diseases may be at increased risk of aseptic meningitis (see below and section “Adverse reactions”).
Dermatological effects
Severe cutaneous adverse reactions (SCARs)
Severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug-induced eosinophilia with systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported with ibuprofen (see section 4.8). The majority of these reactions occurred within the first month of treatment. If signs and symptoms suggestive of these reactions appear, ibuprofen should be discontinued immediately and alternative treatment considered (if necessary).
In exceptional cases, serious skin and soft tissue infections may occur in association with chickenpox. The role of NSAIDs in worsening these infections has not been established. Therefore, it is recommended that ibuprofen be avoided in patients with chickenpox.
Hematological effects
Ibuprofen, like other NSAIDs, can inhibit platelet aggregation and prolong bleeding time in healthy volunteers.
Aseptic meningitis.
Aseptic meningitis has been reported rarely in patients treated with ibuprofen. Although aseptic meningitis is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, cases of aseptic meningitis have been reported in patients without these chronic diseases.
Masking the symptoms of underlying infections.
As with other NSAIDs, ibuprofen may mask the symptoms of an infectious disease, which may delay the initiation of appropriate treatment and thus complicate the course of the disease. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When ibuprofen is used for fever or for the relief of pain in an infection, monitoring for the presence of an infectious disease is recommended. In the setting of outpatient treatment, the patient should consult a doctor if symptoms persist or worsen.
Use during pregnancy or breastfeeding
Fertility
Ibuprofen may impair female fertility and is not recommended for use in women attempting to conceive. Women who have difficulty conceiving or who are undergoing evaluation for infertility should consider discontinuing ibuprofen.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonal/fetal development. Epidemiological data suggest an increased risk of miscarriage, cardiac malformations and gastroschisis following the use of a prostaglandin synthesis inhibitor in early pregnancy. This risk is believed to increase with dose and duration of treatment. In animal studies, the use of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryonal/fetal death. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis. From the 20th week of pregnancy onwards, ibuprofen may cause oligohydramnios due to renal dysfunction in the foetus. This condition may occur shortly after initiation of treatment and is usually reversible upon discontinuation of treatment. In addition, there have been reports of narrowing of the ductus arteriosus following treatment in the second trimester of pregnancy, which in most cases resolved after discontinuation of treatment. Therefore, ibuprofen should be used during the first and second trimesters of pregnancy only if clearly needed. When ibuprofen is used by women attempting to conceive or during the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible. It may be advisable to monitor the fetus for oligohydramnios and narrowing of the ductus arteriosus after exposure to ibuprofen for several days, starting from the 20th week of gestation. The use of ibuprofen-containing medicinal products should be discontinued if oligohydramnios or narrowing of the ductus arteriosus is detected.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus, resulting in:
cardiopulmonary toxicity (premature narrowing/closure of the ductus arteriosus and pulmonary hypertension),
renal dysfunction (see above).
At the end of pregnancy, prostaglandin synthesis inhibitors in the mother and newborn may lead to:
possible prolongation of bleeding time, anti-aggregation effect, which may occur even at very low doses;
suppression of uterine contractions, which can lead to delayed or prolonged labor.
Therefore, ibuprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").
Labor and delivery
It is not recommended to take ibuprofen during labor and delivery.
The onset of labor may be delayed and its duration prolonged, with an increased tendency to hemorrhage in both mother and child.
Breast-feeding
Limited studies have shown that NSAIDs are excreted in breast milk in very low concentrations. The use of NSAIDs in breastfeeding women should be avoided if possible.
Ability to influence reaction speed when driving vehicles or other mechanisms
Taking ibuprofen may negatively affect the reaction speed of patients, which should be remembered when engaging in activities that require increased concentration, such as driving or working with other mechanisms. The effect on the reaction speed is significantly increased when combined with alcohol.
After taking NSAIDs, undesirable effects such as dizziness, drowsiness, malaise/fatigue and visual disturbances are possible. In case of such effects, patients should refrain from driving or operating other mechanisms.
Method of administration and doses
Doses
Undesirable effects can be minimized by using the lowest effective dose for the shortest period of time necessary to control symptoms (see section "Special warnings and precautions for use").
Adults and children aged 12 and over
The recommended dose of BRUFEN® RETARD is two tablets at a time, once a day, preferably in the early evening, well before bedtime. The tablets should be swallowed whole with sufficient liquid. The tablets should not be chewed, divided, crushed or dissolved to avoid discomfort in the oral cavity and throat irritation. In severe or acute conditions, the total daily dose may be increased to three tablets, divided into 2 doses during the day.
Elderly patients
There is an increased risk of serious adverse reactions in elderly patients. If the use of NSAIDs is necessary, the lowest effective dose should be prescribed for the shortest possible period of time. The patient should be regularly monitored for gastrointestinal bleeding during NSAID therapy. In case of impaired renal or hepatic function, the dose should be adjusted individually.
Method of application
For oral use. It is advisable to take during meals or some time after meals. If the drug is taken shortly after meals, the onset of effect may be delayed. Patients with sensitive gastrointestinal tract are recommended to take the drug during meals.
Children.
BRUFEN® RETARD is not intended for use in children under 12 years of age.
Overdose
Signs and symptoms of toxicity have not usually been observed at doses below 100 mg/kg in children and adults. However, supportive measures may be required in some cases. Signs and symptoms of toxicity have been observed in children after doses of 400 mg/kg or more.
Symptoms
In most patients, symptoms of overdose develop within 4–6 hours after taking a significant amount of ibuprofen.
The most common symptoms of overdose include nausea, vomiting, abdominal pain, lethargy and drowsiness. Central nervous system (CNS) effects include headache, tinnitus, dizziness, convulsions and loss of consciousness. Rarely, nystagmus, metabolic acidosis, hypothermia, renal symptoms, gastrointestinal bleeding, coma, apnea, diarrhoea and CNS and respiratory depression have been reported. In severe poisoning, metabolic acidosis and increased prothrombin time/international normalised ratio (INR) may occur, probably due to interaction with circulating clotting factors. Disorientation, agitation, syncope and cardiovascular toxicity including hypotension, bradycardia and tachycardia have been reported.
In case of a significant overdose, kidney failure and liver damage may develop. A significant overdose is usually well tolerated if no other drugs have been taken.
Prolonged use at doses higher than recommended may lead to severe hypokalemia and renal tubular acidosis. Symptoms may include decreased level of consciousness and general weakness (see sections 4.4 and 4.8).
Treatment
There is no specific antidote for ibuprofen overdose. Treatment should be symptomatic if necessary. Activated charcoal should be administered within one hour of ingestion of a potentially toxic amount. If the dose of the drug exceeds 400 mg/kg, gastric lavage/emptying is recommended within one hour of ingestion, followed by supportive measures.
Ensure sufficient diuresis.
Kidney and liver function should be closely monitored. If necessary, the serum electrolyte balance should be corrected.
After ingestion of a potentially toxic amount of the drug, the patient should be observed for at least four hours.
Frequent or prolonged seizures should be treated with intravenous diazepam. Other measures may be indicated based on the patient's clinical condition.
For the most up-to-date information, contact your local poison control center.
Side effects
The nature of adverse reactions to ibuprofen is similar to those with other NSAIDs.
Gastrointestinal tract
Gastrointestinal adverse reactions are the most common. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, especially in the elderly (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, gastrointestinal bleeding and exacerbation of colitis and Crohn's disease have been reported with ibuprofen (see section "Contraindications"). Gastritis, duodenal ulcer, gastric ulcer and gastrointestinal perforation have been reported less frequently.
On the part of the immune system
Hypersensitivity reactions have been reported with NSAIDs. These include: non-specific allergic reactions and anaphylaxis; airway reactivity including asthma, exacerbation of asthma, bronchospasm or dyspnoea; various skin manifestations including rash of various types, pruritus, urticaria, purpura, angioedema and very rarely erythema multiforme, bullous dermatoses (including Stevens-Johnson syndrome and toxic epidermal necrolysis).
Cardiovascular system
Oedema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical trial data suggest that the use of ibuprofen, particularly at high doses (2400 mg/day), may slightly increase the risk of arterial thrombotic events such as myocardial infarction or stroke (see section 4.4).
Infections and infestations
Rhinitis and aseptic meningitis (especially in patients with pre-existing autoimmune disorders such as systemic lupus erythematosus and mixed connective tissue diseases) with symptoms of stiff neck, headache, nausea, vomiting, fever or disorientation (see section "Special warnings and precautions for use").
Cases of exacerbation of infectious skin inflammations (e.g. necrotizing fasciitis) have been described during the use of NSAIDs. If signs of infection appear or worsen during the use of ibuprofen, the patient should immediately consult a doctor.
Skin and subcutaneous tissue damage
In exceptional cases, severe skin infections and soft tissue complications may occur in association with chickenpox (see also "Infections and Invasions").
The following adverse reactions are listed, which may be associated with ibuprofen, and are classified by frequency and MedDRA system organ class.
Infections and infestations: uncommon - rhinitis; rare - aseptic meningitis (see section "Special warnings and precautions for use").
From the blood and lymphatic system: rare - leukopenia, thrombocytopenia, neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia.
On the part of the immune system: infrequent - hypersensitivity; rare - anaphylactic reaction.
On the part of the psyche: infrequent - insomnia, anxiety disorders; rare - depression, confusion.
From the nervous system: frequent - headache, dizziness; infrequent - paresthesia, drowsiness; rare - optic neuritis.
On the part of the organs of vision: infrequent - visual impairment; rare - toxic optic neuropathy.
From the side of the organs of hearing and vestibular apparatus: infrequent - hearing impairment, tinnitus, vertigo.
Respiratory, thoracic and mediastinal disorders: uncommon – bronchial asthma, bronchospasm, dyspnoea.
From the digestive system: frequent - dyspepsia, diarrhea, nausea, vomiting, abdominal pain, flatulence, constipation, melena, hematemesis, gastrointestinal bleeding; infrequent - gastritis, duodenal ulcer, gastric ulcer, ulcerative stomatitis, gastrointestinal perforation; very rare - pancreatitis; unknown frequency - exacerbation of colitis and Crohn's disease.
Hepatobiliary system: infrequent - hepatitis, jaundice, liver dysfunction; very rare - liver failure.
Skin and subcutaneous tissue disorders: common: rash; uncommon: urticaria, pruritus, purpura, angioedema; very rare: severe cutaneous adverse reactions (SCARs) (including erythema multiforme, exfoliative dermatitis, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis); frequency unknown: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), acute generalized exanthematous pustulosis (AGEP), photosensitivity reactions.
Metabolism and nutrition disorders: frequency unknown - decreased appetite, hypokalemia*.
From the urinary system: infrequently - toxic nephropathy in various forms, including tubulointerstitial nephritis, nephrotic syndrome and renal failure; very rare - acute renal failure; frequency unknown - ureteral colic, dysuria, renal tubular acidosis*.
General disorders and administration site conditions: common: malaise/fatigue; rare: edema.
From the side of the cardiovascular system: very rare - heart failure, myocardial infarction (see also the section "Special instructions for use"); unknown frequency - Kounis syndrome.
From the vascular system: very rare - arterial hypertension.
*Renal tubular acidosis and hypokalemia have been reported during the post-marketing period, usually after prolonged use of ibuprofen at doses higher than recommended.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C, out of the reach of children.
Packaging
10 tablets in a blister, 1 or 2 blisters in a cardboard box; 14 tablets in a blister, 1 blister in a cardboard box.
Vacation category
According to the recipe.
Producer
Famar A.V.E. Anthoussa Plant, Greece/ Famar AVE Anthoussa Plant, Greece.
Location of the manufacturer and address of its place of business. Anthousa Avenue 7, Anthousa Attiki, 15349, Greece.
